Background: We previously demonstrated that the reduced expression in immortalized cells (REIC)/dikkopf-3 (Dkk-3) gene was downregulated in various malignant tumors, and that an adenovirus vector carrying the REIC/Dkk-3 gene, termed Ad-REIC induced cancer-selective apoptosis in pancreatic cancer and hepatocellular carcinoma.
Objective: In this study, we examined the therapeutic effects of Ad-REIC in biliary cancer using a second- generation Ad-REIC (Ad-SGE-REIC).
Methods: Human biliary cancer cell lines (G-415, TFK-1) were used in this study. The cell viability and apoptotic effect of Ad-SGE-REIC were assessed in vitro using an MTT assay and Hoechst staining. The anti-tumor effect in vivo was assessed in a mouse xenograft model. We also assessed the therapeutic effects of Ad-SGE-REIC therapy with cisplatin. Cell signaling was assessed by Western blotting.
Results: Ad-SGE-REIC reduced cell viability, and induced apoptosis in biliary cancer cell lines via the activation of the c-Jun N-terminal kinase pathway. Ad-SGE-REIC also inhibited tumor growth in a mouse xenograft model. This effect was further enhanced in combination with cisplatin.
Conclusion: Ad-SGE-REIC induced apoptosis and inhibited tumor growth in biliary cancer cells. REIC/Dkk-3 gene therapy using Ad-SGE-REIC is an attractive therapeutic tool for biliary cancer.
[http://dx.doi.org/10.1093/jjco/hyv213] [PMID: 27025903]
[http://dx.doi.org/10.1158/0008-5472.CAN-08-0080] [PMID: 18922905]
[http://dx.doi.org/10.1111/jgh.13259] [PMID: 26643412]
[http://dx.doi.org/10.1186/s40425-019-0692-z] [PMID: 31383016]